Crystal structure of Staphylococcus aureus Zn-glyoxalase I: new subfamily of glyoxalase I family. Issue 2 (25th January 2018)

• Record Type: Journal Article
• Authors: Chirgadze, Yuri N.; Boshkova, Eugenia A.; Battaile, Kevin P.; Mendes, Vitor G.; Lam, Robert; Chan, Tiffany S.Y.; Romanov, Vladimir; Pai, Emil F.; Chirgadze, Nickolay Y.
• Is Part Of: Journal of biomolecular structure & dynamics. Volume 36:Issue 2(2018)
• Page Start: 376
• Page End: 386
• Publication Date: 2018-01-25
• Subjects: metalloprotein -- glyoxalase I -- subfamily -- pathogen; Biomolecules -- Periodicals; Molecular structure -- Periodicals; Molecular Biology -- Periodicals; Biomechanics -- Periodicals; 572
• DOI: 10.1080/07391102.2016.1278038
• Languages: English
• ISSNs: 0739-1102

Abstract

Abstract : The crystal structures of protein SA0856 from Staphylococcus aureus in its apo-form and in complex with a Zn 2+ -ion have been presented. The 152 amino acid protein consists of two similar domains with α + β topology. In both crystalline state and in solution, the protein forms a dimer with monomers related by a twofold pseudo-symmetry rotation axis. A sequence homology search identified the protein as a member of the structural family Glyoxalase I. We have shown that the enzyme possesses glyoxalase I activity in the presence of Zn 2+, Mg 2+, Ni 2+, and Co 2+, in this order of preference. Sequence and structure comparisons revealed that human glyoxalase I should be assigned to a subfamily A, while S. aureus glyoxalase I represents a new subfamily B, which includes also proteins from other bacteria. Both subfamilies have a similar protein chain fold but rather diverse sequences. The active sites of human and staphylococcus glyoxalases I are also different: the former contains one Zn-ion per chain; the latter incorporates two of these ions. In the active site of SA0856, the first Zn-ion is well coordinated by His58, Glu60 from basic molecule and Glu40*, His44* from adjacent symmetry-related molecule. The second Zn3-ion is coordinated only by residue His143 from protein molecule and one acetate ion. We suggest that only single Zn1-ion plays the role of catalytic center. The newly found differences between the two subfamilies could guide the design of new drugs against S. aureus, an important pathogenic micro-organism .